Dermatitis Herpetiformis
A 53-year-old white man presents with a very pruritic rash on his elbows, knees, buttocks, arms, and legs for at least 2 months duration (Figure 1-3).
History. He has a history of chronic diverticulitis, treated surgically 2 years prior with a post-surgical infection. He has a history of asthma and chronic sinusitis, for which he underwent sinus surgery several months ago. He was exposed to sedatives and approximately 1 week of antibiotics at the time. Subsequent to this episode and exposure, the patient suddenly developed the pruritic rash on the areas described.
Physical examination. The patient was a well-appearing man with annular, scaly erythematous subacute, pseudovesicular lesions on the elbows, knees, buttocks, and proximal arms and legs. Most of the lesions were excoriated on the knees, proximal thighs, and natal crease. The patient’s head and distal extremities were clear. No burrows or lymphadenopathy were evident.
He denied weight loss, night sweats, fatigue, abdominal pain, cramping, nausea, vomiting, constipation, or diarrhea. He had no known drug allergies.
Diagnosis. Dermatitis herpetiformis (DH) was suspected, with other bullous (eg, linear IgA dermatosis and bullous pemphigoid) or allergic conditions considered.
Treatment. Symptoms were initially managed with diphenhydramine, cetirizine, and topical clobetasol ointment until the diagnosis was confirmed and baseline blood work obtained. Skin biopsies performed for hematoxylin and eosin staining and direct immunofluorescence microscopy both supported the diagnosis of DH.
With normal baseline blood work (liver and renal function, glucose 6 dehydrogenase (G6PD) levels, and baseline complete blood count), dapsone 25 mg bid was initiated.
The patient tolerated the drug well and lesions showed improvement within 1 day. Additionally, the patient was counseled regarding a gluten free diet (GFD) and referred to a dietician and gastroenterologist, both of which he has delayed in pursuing.
Discussion. DH, also known as Duhring’s disease, is a rare blistering skin disorder considered the cutaneous manifestation of celiac disease (CD). Both conditions result from an immune reaction to ingested gliadin, the protein component of gluten, which stimulates IgA antibodies against tissue transglutaminase (tTG), an enzyme localized to the gut. In DH, IgA autoantibodies cross-react with epidermal transglutaminase 3 (e-TG3), a homologous enzyme to tTG found in the epidermis, causing a chronic pruritic, blistering skin disorder.1 Granular IgA /e-TG3 complexes deposit at the papillary dermis, activating complement and eliciting neutrophilic infiltrates that lead to subepidermal blisters.1
DH’s mean age of onset is the fourth decade, it affects whites more frequently, and is associated with a variety of autoimmune conditions, including Hashimoto’s thyroiditis and systemic lupus erythematosus.2 While multiple HLA antigens have been linked to the condition,3-6 dietary gluten plays a primary role in disease pathogenesis and progression.7
The presentation of DH can be difficult to distinguish from other dermatoses. DH presents in a characteristic distribution involving extensor forearms, elbows, knees, back and buttocks. The presentation in this patient was classic in both the age affected and distribution of lesions. The lesions can be pleomorphic (eg, urticarial papules, vesicles, plaques) and tend to elicit severe pruritus. Most lesions are excoriated by the time of examination.3 Histology of affected skin in DH reveals a characteristic papillary edema with a predominantly neutrophilic infiltrate; however, visualization with direct immunofluorescence is considered the gold standard for diagnosis.
DH characteristically flares with halide exposure and responds rapidly to dapsone therapy. Ideally, DH is treated with a GFD, however, this is not easy to adhere to. Furthermore, even with strict adherence to a GFD, it can take months to eliminate skin lesions.8 A combination of lifestyle modification and pharmacologic therapy with dapsone is thus initiated with the goal of long-term dietary control and dapsone tapering. Dapsone rapidly resolves pruritis within 72 hours and heals active skin lesions within days.2,9 Therapy requires close monitoring because of side effects, including methemoglobinemia, hemolytic anemia (especially with G6PD deficiency), and leukopenia.10 Other sulfa-based drugs have also been effective.
DH is a chronic disorder that tends to persist for life and mandates continuous intervention.11 Symptoms usually recur 2 days after dapsone withdrawal and within 3 months of gluten consumption.12,13 Importantly, a lifelong GFD may protect against increased lymphoma risks in untreated DH (and CD) patients, including enteropathy-associated T-cell lymphoma.14-16 Though DH varies in severity and onset, it is important to recognize its symptoms. Proper dietary modification and treatment controls symptoms exceptionally well and prevents complications including lymphoma and overt CD.
Outcome of the case. After being asymptomatic after 1 month on dapsone and dietary intervention, the patient discontinued the dapsone on his own, only to have a skin flare. Reinstitution of the dapsone cleared his skin rapidly. The patient currently has residual erythema on the elbows, but no active lesions.
References:
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